tbuckley/cabot-search huggingface dataset:
Assessment of risk of overall and late distant recurrence by Breast Cancer Index in postmenopausal women with early-stage, HR+ breast cancer in the TEAM trial.
Authors: John MS Bartlett, Keying Xu, Jenna Wong, Gregory Russell Pond, Yi Zhang, Melanie Spears, Ranelle C. Salunga, Elizabeth Mallon, Karen J Taylor, Annette Hasenburg, Christos Markopoulos, Luc Yves Dirix, Caroline M. Seynaeve, Cornelis J.H. Van De Velde, Daniel William Rea, Catherine A Schnabel, Kai Treuner, Jane Bayani
Journal: Journal of Clinical Oncology (2023)

509 Background: Individual risk assessment of distant recurrence (DR) is particularly relevant for early-stage HR+ breast cancer patients, as they face a prolonged risk of recurrence even after adjuvant endocrine therapy. Previously, we have shown that the Breast Cancer Index (BCI) and BCIN+ risk groups are significantly prognostic for risk of overall (0-10y) and late (5-10y) distant recurrence in N0 and N1 breast cancer patients, respectively, enrolled in the Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial. Here, the prognostic performance of BCI and BCIN+ as a continuous risk score for overall and late distant recurrence was evaluated in the TEAM trial. Methods: BCI testing was performed blinded to clinical outcome with BCI/BCIN+ risk scores calculated as previously described. Cox proportional hazard models adjusted for age, tumor size, grade and treatments were used to estimate hazard ratios (HRs) and the associated 95% confidence intervals (CIs) for BCI/ BCIN+ continuous risk scores. The 10y risk of overall and late DR were estimated as a function of risk scores from the Cox models using Breslow estimates. Results: Continuous risk curves for overall and late DR were obtained in patients who did not receive adjuvant chemotherapy and those who remained DR-free at 5 years regardless of chemotherapy, respectively, to reflect the two key time points for breast cancer treatment decision-making. InN0 patients not treated with chemotherapy (N = 1197), BCI was significantly prognostic for overall DR with a HR of 1.39 (95% CI 1.25-1.54; p &lt; 0.001), while BCIN+ was significantly prognostic in N1 patients who did not receive chemotherapy (N = 1319) with a HR of 4.29 (95% CI 2.93-6.28; p &lt; 0.001). Among patients who remained DR-free at 5 years, in the N0 subset (N = 1285), BCI was significantly prognostic for late DR with a HR of 1.23 (95% CI 1.07-1.42; p &lt; 0.001), while BCIN+ remained to be significantly prognostic in the N1 subset (N = 1762) with a HR of 2.78 (95% CI 1.75-4.43; p &lt; 0.001). Similar results were observed in the HER2- subset for both overall and late DR. Continuous risk curves for BCI and BCIN+ for overall and late DR showed an increasing risk of DR with higher BCI/BCIN+ scores. Conclusions: Results from this largest BCI study to date further support the use of BCI to provide individualized risk estimates for both overall and late DR in women with HR+ breast cancer to aid in personalized decision-making for adjuvant therapy. [Table: see text]
Team-based versus technology-based supportive cancer care (SCC): Assessment of implementation across 24 different clinical settings.
Authors: Sacha Moufarrej, Marika S. Mathew, Emily H. Wood, Hector S. Medrano, Cynthia C. Perez, Keely E. Fuller, Madhuri Agrawal, Manali I. Patel
Journal: Journal of Clinical Oncology (2023)

1528 Background: Advanced care planning and symptom management, otherwise known as Supportive Cancer Care (SCC), are fundamental services that patients should receive after a cancer diagnosis. We launched a 24-clinic site cluster randomized clinical trial in July 2022 comparing two SCC delivery approaches: a team-based intervention in which patients engage in advanced care planning and symptom assessments with a lay health worker versus a technology-based intervention in which patients receive internet-based SCC education. The preliminary aim of this study is to evaluate clinic characteristics that may impact implementation and effectiveness of these SCC delivery approaches. Methods: We invited study staff at all 24 sites, including community oncology clinics, Kaiser Permanente clinics, Veterans Affairs facilities, safety-net hospitals, and academic centers, to participate in a survey and semi-structured interview. We used Consolidated Framework for Implementation Research (CFIR) and Reach, Effectiveness, Adoption, and Implementation (RE-AIM) frameworks to assess organizational culture, readiness, facilitators, and barriers to SCC delivery. Surveys were analyzed using descriptive statistics; interviews were analyzed using thematic analysis. Results: Among 30 interview participants across 24 clinics, of which 23 completed surveys, 9 (30%) were clinic principal investigators, 11 (36.7%) were research staff, and 10 (33.3%) were implementation staff. Survey respondents implementing team-based SCC were more confident that their approach: 1) accounted for patient care preferences (93.3%) and 2) had strong evidence (86.7%) than respondents implementing technology-based SCC (62.5% and 25.0% respectively). More respondents implementing team-based SCC expressed confidence in organization leadership (100%) and adequate resources for SCC (86.7%) than respondents implementing technology-based SCC (75.0%). Among interview participants, team-based approaches for SCC delivery were considered more effective, as they could: 1) reduce time burden for clinicians 2) tailor delivery to patient preferences; and 3) increase patient support. Participants believed that team-based approaches would also be more difficult and costly to implement. Barriers to both SCC delivery approaches include: a) limited technology access for patients, b) competing organization priorities which limit staffing and funding for SCC, and c) information overload for patients and caregivers. Conclusions: Implementation of SCC delivery approaches is needed but requires organizational leadership and implementation resources. Team-based approaches are considered more effective, but barriers such as staffing and funding may inhibit the scalability. Implementation evaluations are crucial to understand real-world applicability and scalability of SCC delivery.
Using SMS technology to improve quality of life and symptom management in the breast cancer patient population: A feasibility study.
Authors: Tracy Fulton, Laura Lettkeman, Thomas A. Buchholz
Journal: Journal of Clinical Oncology (2023)

e13619 Background: Cancer patients experience a wide range of negative side effects/symptoms from chemotherapy and radiation including pain, dehydration, nausea/vomiting, and diarrhea/constipation. Symptoms are distressing and decrease the overall quality of life and increase unnecessary hospitalizations and emergency visits. Symptom management and quality of life may be improved by using Short Message System (SMS) texting in cardiac and diabetic patient populations. The technology may also decrease costs for unnecessary emergency department (ED) visits by breast cancer patients. The purpose of this study was to determine if an SMS texting service can improve quality of life by improving symptom management. A secondary purpose was to evaluate if texting decreases emergency visits by breast cancer patients. Methods: This IRB-approved, consented study implemented an SMS texting program for breast cancer patients. Participants received two texts per day during their chemotherapy treatment period (6 months), one text being informational regarding symptom management and the second was one of encouragement and inspiration. Participants were called bi-weekly to complete the Distress Thermometer for Patients (NCCN). ED visits and/or hospital admission rates for the sample were collected. An exit interview measured satisfaction with the program in quantitative measures and theme analysis for qualitative measures. Twenty patients participated in this study, with 13 included in the data analysis. Results: SMS texting provided a change in treatment for symptom management in 40% of patients. Overall satisfaction with the SMS program was at the 89 th percentile. Almost all participants felt supported and cared for due to bi-weekly calls by the investigators. Only 10% of the participants visited the emergency department, which is lower than historical averages. Data concerning the distress thermometer proved to be non-informative. Conclusions: SMS texting is feasible and easily integrated into the care of breast cancer patients. Texting technology may provide engagement with the care team leading to changes and improvement in symptom management during chemotherapy treatment. Further study of texting technology providing interactive abilities for patient-reported outcomes is warranted.
ORACLE-RIPA study: A phase II, randomized, open-label, parallel-group study comparing the immune modulation effect of neoadjuvant ribociclib, palbociclib, and abemaciclib in early ER+/HER2- breast cancer.
Authors: I-Chun Chen, Ching-Hung Lin, Dwan-Ying Chang, Tom Wei-Wu Chen, Wei-li Ma, Ming-Yang Wang, Yen-Shen Lu
Journal: Journal of Clinical Oncology (2023)

TPS632 Background: CDK4/6 inhibitors (CDK4/6i), ribociclib, palbociclib, and abemaciclib, provide similar progression-free survival (PFS) benefits when combined with endocrine therapy in ER+/HER2- metastatic breast cancer (MBC) patients. However, not all CDK4/6i have demonstrated overall-survival (OS) benefits in their respective phase III trials. Both, ribociclib and abemaciclib, have shown significant OS benefits in ER+/HER2- MBC patients, but palbociclib has not. Because of similar benefits of the 3 CDK4/6i on PFS, the OS benefit is likely not a result of differences in their synergistic efficacy of a CDK4/6i with endocrine therapy. CDK4 inhibition on cancer cells can also result in upregulation of MHC-I and MHC-II expression on cell surface and Rb-dependent interferon-gamma secretion. CDK6 inhibition might inhibit T cell and NK cell proliferation causing a negative effect on the tumor microenvironment. CDK6 inhibition can also reduce regulatory T cell numbers and increase cytokine production to enhance cytotoxic T cell function. Thus, we hypothesize that the differential impact of the 3 CDK4/6i on OS might be resulting from different immunomodulation effects. To investigate the functional alterations of the CDK4/6i on the BC microenvironment, the neoadjuvant treatment setting is best to compare the immune modulation effects of CDK4/6i from pre-treatment and post-treatment tumor tissues. Methods: This phase II multicenter, randomized, open-label, parallel-group study evaluates the immunomodulation effects of the 3 different CDK4/6i (ribociclib, palbociclib, or abemaciclib) combined with letrozole in neoadjuvant early ER+/HER2- breast cancer patients. A total of 20 patients will be enrolled into each treatment arm. The major inclusion criteria are female patients aged ≥ 20 years old, having a histologically and/or cytologically confirmed diagnosis of ER+ ( &gt; 10%) and/or PR+, HER2 negative (IHC 0+/1+, or IHC 2+ plus FISH negative) breast cancer, stage II/III, and adequate organ function. The treatment will12 weeks of letrozole plus a CDK4/6i. Premenopausal patients will receive GnRH agonist. Breast tumor biopsy, blood and stool samples will be collected prospectively at the time prior to treatment initiation, at 2 weeks after treatment, and at surgery. A description summary will be utilized to compare the results between the 3 CDK4/6i. The trial results will address questions about differences or similarities of the 3 CDK4/6i within the same study. The study is currently enrolling at 3 medical centers s in Taiwan. Clinical trial information: Pending formal number assignment .
Pyrotinib plus capecitabine for patients with HER2-positive metastatic breast cancer and brain metastases: 3-year follow-up results from the phase 2 PERMEATE trial.
Authors: Min Yan, Quchang Ouyang, Tao Sun, Limin Niu, Jin Yang, Li Li, Yuhua Song, Chunfang Hao, Zhanhong Chen
Journal: Journal of Clinical Oncology (2023)

1048 Background: HER2-positive metastatic breast cancer has a high risk of brain metastases, leading to poor survival. Our phase 2 PERMEATE trial (NCT03691051) has shown the promising efficacy of pyrotinib (an irreversible pan-HER receptor tyrosine kinase inhibitor) plus capecitabine in patients with HER2-positive metastatic breast cancer and brain metastases, with an intracranial objective response rate of 74.6% (44/59) and 42.1% (8/19) in patients with radiotherapy-naïve (cohort A) and radiotherapy-treated (cohort B) brain metastases, respectively. Here we updated 3-year follow-up results from this trial. Methods: Patients received 21-day cycles of pyrotinib (400 mg orally once daily) and capecitabine (1000 mg/m 2 orally twice daily on days 1-14) until disease progression or intolerable toxicity. Patients with progression isolated to the brain lesions would be withdrawn from the study, but could resume on the study treatment after local surgery or radiotherapy until the second progression at any site or death, at the discretion of the investigator. Intracranial and extracranial responses were assessed according to the Response Evaluation Criteria In Solid Tumors, version 1.1. Progression-free survival (PFS; time from the initiation of the study treatment to progression at any site or any-cause death), overall survival (OS), and second PFS (PFS2; time from progression isolated to the brain lesions to the second progression at any site) were reported. Results: By the data cutoff date on February 8, 2023, the median follow-up duration was 40.5 months (95% CI: 39.0-43.0). Cohort A showed a median PFS of 10.7 months (95% CI: 7.6-14.9) and a median OS of 35.9 months (95% CI: 25.1-not reached). The 1-year and 3-year OS rates were 84.6% (95% CI: 76.0-94.4) and 49.8% (95% CI: 38.0-64.6), respectively. Fifteen patients with progression isolated to the brain lesions in cohort A resumed on the study treatment after local treatment, with a median PFS2 of 10.4 months (95% CI: 6.5-19.7). Cohort B showed a median PFS of 5.6 months (95% CI: 5.4-11.9) and a median OS of 31.4 months (95% CI: 22.0-not reached). The 1-year and 3-year OS rates were 78.9% (95% CI: 64.0-99.6) and 29.1% (95% CI: 13.0-60.4), respectively. Conclusions: These findings suggest the long-term survival benefit provided by pyrotinib plus capecitabine in patients with HER2-positive metastatic breast cancer and brain metastases, especially in the radiotherapy-naive cohort. Clinical trial information: NCT03691051 .
A disease registry study to prospectively observe treatment patterns and outcomes in patients with HER2+ unresectable locally advanced or metastatic breast cancer (aBC): Interim results of the ESTHER study (NCT02393924).
Authors: Catherine Harper-Wynne, James Owen, Galina Velikova, Stephanie Sutherland, Mircea Jivulescu, Alistair E. Ring
Journal: Journal of Clinical Oncology (2023)

e13039 Background: Over the last decade the standard-of-care treatment for patients with HER2+ aBC has included anti-HER2 therapies often combined with chemotherapy. These approaches have shown efficacy in clinical trials which have recruited patients in restricted populations defined by lines of therapy and previous treatments. There are few data regarding the long-term outcomes of patients treated with these regimens, including those with brain metastases. We conducted a prospective, multicentre non-interventional study to observe anti-cancer treatment regimens and clinical outcomes in patients with HER2 positive aBC. Methods: Adult patients diagnosed with HER2-positive aBC within the last 6 months were included. No specific treatment approach or course was mandated by the protocol. Source data was taken from the patient’s chart and other medical records, then reported by means of an electronic data collection system. Data regarding treatment received, efficacy (progression-free and overall survival (PFS), response rates (RR) and development of CNS metastases) and safety (including cardiac toxicity) were captured. Results: Between February 2015 and April 2018, 311 eligible patients were recruited with median age 57 years (24-96). At diagnosis of aBC the most common distant metastatic sites were bone (n = 145;47%), liver (n=117;38%), lung (n=100;32%) and brain (n=21;7%). First line treatment was with pertuzumab (P)/trastuzumab(T)/chemotherapy (n=212;68%), T/chemotherapy (n=45;14%), other T combinations without P (n=19;6%), Trastuzumab Emtansine regimens without T or P (n=16;5%) (19; 5% other combinations). Patients’ status as of cut-off date for this analysis (28 th Feb 2022, median follow-up 44.1 months) is shown. The median PFS of patients treated in the 1 st , 2 nd and 3 rd lines was 26.7 months, 10.7 months and 8.6 months. At the time of this analysis an additional 60 patients (19%) had developed brain metastases during first line. The number of patients starting 2nd, 3 rd and 4th line treatment with brain metastases were 28 (22%), 17 (40%), 7 (37%) respectively. Conclusions: In routine clinical practice, as reflected by this registry, at least 40% of patients who initiate first line therapy for advanced breast cancer do not proceed to 3 rd line therapy, and brain metastases become increasingly common. These findings have implications for selection of optimal 2 nd and 3 rd line treatment. Clinical trial information: ISRCTN02393924 . [Table: see text]
Homologous recombination deficiency (HRD) status to predict the efficacy and prognosis of platinum-based neoadjuvant chemotherapy in patients with triple-negative breast cancer.
Authors: Xuan Jin, Minyan Chen, Hanxi Chen, Lili Chen, Yuxiang Lin, Long Wu, Ganghuai Tang, Weiwei Li, Zhan Huang, Qian Li, Changbin Zhu, Wenhui Guo, Fangmeng Fu, Chuan Wang
Journal: Journal of Clinical Oncology (2023)

e12605 Background: Triple negative breast cancer (TNBC) is the most aggressive type of breast cancer, and the predictive role of homologous recombination deficiency (HRD) in TNBC treated with platinum-based neoadjuvant chemotherapy (NCT) is not well described. Here, we sought to assess the association of HRD with pathological complete response (pCR) and survival outcomes in TNBC patients treated with NCT. Methods: 123 patients with stage II to III TNBC received one type of NCT regimen, including paclitaxel followed by anthracycline and cyclophosphamide-based NCT, and platinum-based NCT were enrolled in this study. The optimal cutoff of HRD score was determined by the Youden’s index on the ROC curve. HRD status was defined by either HRD score ≥ threshold or BRCA1/2 [tumor BRCA (t BRCA) and/or germline BRCA (g BRCA)] mutation. Logistic regression analysis was used to analyze the relationship between HRD and pCR. The Kaplan-Meier method, log-rank test and Cox regression were used for survival analysis. Results: A total of 104 FFPE and paired blood samples were successfully profiled from the 123 patients. The optimal cutoff for the HRD score of 58 was calculated based on the maximum Youden index value (0.235). HRD-High (HRD-H) was defined by either HRD score ≥ 58 or BRCA1/2 mutation. Of the 104 patients, 11.54 % (12) demonstrated BRCA mutation (g BRCA1 = 4, g BRCA2 = 4, t BRCA1=2 and t BRCA2 = 2), and another 46.15% (48) demonstrated HRD-H. In univariate logistic regression analysis, HRD status was significantly associated with a better pCR (p = 0.025, OR = 3.071, 95% CI: 1.154-8.175). Patients with HRD-H (p = 0.0103) or BRCA1/2 mutation (p = 0.0199) were all associated with superior event-free survival (EFS). There was a trend toward improved distant disease-free survival (DDFS), breast cancer–specific survival (BCSS), and overall survival (OS) in patients with HRD-H or BRCA1/2 mutation compared with HRD-Low or BRCA1/2 wild-type, although the differences did not reach statistical significance. Homologous recombination repair (HRR)-related genes mutation status was only associated with EFS (p = 0.0458). In multivariate logistic regression, Stromal tumor-infiltrating lymphocytes (sTILs) (p = 0.033, OR = 3.134, 95% CI:1.096-8.963) and HRD status (p = 0.015, OR = 4.014, 95% CI: 1.306-12.332) were both significantly associated with pCR. Conclusions: TNBC patients with HRD-H or BRCA1/2 mutation were more likely to benefit from platinum-based standard NCT.
An analysis of National Cancer Data Base: Male breast cancer and overall survival.
Authors: Sara Albagoush, Durva Masih, Xinxin Wu, Michelle Swedek, Saboor Ejaz Randhawa, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2023)

e12513 Background: Male breast cancer unlike female breast cancer is rare, representing approximately 1% of cancers that occur in men and approximately 1% of all BCs worldwide. It is managed by extrapolating from breast cancer in women due to it is rarity. We aimed to perform a large retrospective study with a focus on disease characteristics and overall survival. Methods: We performed a retrospective analysis of male breast cancer patients from the National Cancer Database (2004–2020). We obtained demographic, tumor, clinical and therapy data. Kaplan-Meier survival curves were created to estimate overall survival. Cox regression analysis was used to compare the groups within each variable. Results: We identified 31348 patients with primary diagnosis of male breast cancer (median age 66 years). Patients were predominantly white (82.1%) then black (13.4%). Most of patients are located in urban or metropolitan areas (95.9%) within a median of only 8.4 miles from the hospital where they received care. Almost equal patients treated at community hospitals (48.2%) and academic hospitals (50%). Patients were mainly covered by Medicare (49.0%) then Private insurance (40.8%). Most men who diagnosed with MBC had invasive cancer (88.3%). Only 1433 (4.6%) patients presented with metastases at diagnosis. The median tumor size was 3 cm. Most of tumors were moderately differentiated (36.1%) then (24.0%) poorly differentiated. In most patients, the tumor is present in the central portion of the breast. Several treatment modalities were used, of which primary surgical resection was the most common [90.7%). Among systemic therapies, hormonal therapy was the most common (57.1%%) then chemotherapy (34.3%) then radiation therapy (30.6%) and immunotherapy (4.8%). In terms of duration, time from diagnosis to surgery was 26 days (shortest), diagnosis to immunotherapy was 57 days, diagnosis to chemotherapy was 59 days, and time from diagnosis to radiation was 145 days (longest). The overall 30-day mortality was 0.3% (75/26333), the 90-day mortality was 0.9% (224/26333). Median overall survival is 67.1% (95% CI 143.371-150.349). Using cox proportional hazards model; factors influencing survival rate including Age, race, CDS P &lt; 0.001, tumor size, year of diagnosis P &lt; 0.000. All treatment modalities including surgery, chemotherapy and hormonal therapy was associated with increase overall survival with P &lt; 0.001 (95% CI 1.245-1.370). Conclusions: This is the largest study to date on epidemiology and prognostic factors for MBC using NCDB. Old age, white race, greater comorbidity index, and larger tumor size are associated with decreased survival. Surgery and adjuvant therapy are associated with increased overall survival. Further studies warranted to elucidate the causes of improved survival associated with some of these factors will help improve quality of care for patients with MBC.